1. Field of the Invention
The present invention relates to the use of creatine and/or creatine derivatives and/or creatinine and/or creatinine derivatives in cosmetic or dermatological preparations for the treatment and prophylaxis of the symptoms of UV and/or ozone-induced skin damage and of inflammatory and degenerative skin conditions.
2. Discussion of Background Information
Cosmetic skin care is primarily understood to mean strengthening or restoring the natural function of the skin as a barrier against environmental influences (for example, dirt, chemicals, microorganisms) and against the loss of endogenous substances (for example, water, natural fats, electrolytes).
Impairment of this function may lead to increased resorption of toxic or allergenic substances or to attack by microorganisms, resulting in toxic or allergic skin reactions.
Another aim of skin care is to compensate for the loss by the skin of sebum and water caused by daily washing. This is particularly important if the natural regeneration ability is inadequate. Furthermore, skin care products should protect against environmental influences, in particular against sun and wind, and delay skin aging.
Chronological skin aging is caused, for example, by endogenous, genetically determined factors. The following structural damage and functional disorders can arise, also under the term “senile xerosis”, for example, in the epidermis and the dermis as a result of aging:                a) Dryness, roughness and formation of dryness wrinkles,        b) Itching and altered pore structure of the skin        c) Reduced regreasing by sebaceous glands (e.g. after washing).        
Exogenous factors, such as UV light and chemical noxae, can have a cumulative effect and, for example, accelerate or supplement the endogenous aging processes. In the epidermis and dermis, for example, the following structural damage and functional disorders arise in the skin in particular as a result of exogenous factors; these are more far-reaching than the degree and quality of the damage in the case of chronological aging:                d) Visible vascular dilation (teleangiectases, cuperosis);        e) Flaccidity and formation of wrinkles;        f) Local hyperpigmentation, hypopigmentation and abnormal pigmentation (e.g., senile keratoses) and        g) Increased susceptibility to mechanical stress (e.g., cracking).        
The present invention relates in particular to products for the care of skin that has aged naturally and to the treatment of secondary damage from light-aging, in particular the phenomena listed under a) through g).
Products for the care of aged skin are known per se. They comprise, for example, retinoids (vitamin A acid and/or derivatives thereof) or vitamin A and/or derivatives thereof. Their effect on structural damage is, however, limited. Furthermore, in product development, there are considerable difficulties in stabilizing the active ingredients to an adequate extent against oxidative decay. The use of products containing vitamin A acid, moreover, often causes severe erythematous skin irritations. Retinoids can therefore only be used in low concentrations.
In particular, the present invention relates to cosmetic preparations with an effective protection against harmful oxidation processes in the skin, but also to the protection of cosmetic preparations themselves or to the protection of the constituents of cosmetic preparations against harmful oxidation processes.
The harmful effect of the ultraviolet part of solar radiation on the skin is generally known. Whereas rays with a wavelength of less than about 290 nm (the so-called UVC range) are absorbed by the ozone layer in the earth's atmosphere, rays in the range between about 290 nm and about 320 nm, the so-called UVB range, cause erythema, simple sunburn or even burns of greater or lesser severity.
The narrower range around 308 nm is indicated to be the maximum of the erythematous effect of sunlight.
Numerous compounds are known for protecting against UVB radiation; these are derivatives of 3-benzylidene camphor, of 4-aminobenzoic acid, of cinnamic acid, of salicylic acid, of benzophenone and also of 2-phenylbenzimidazole.
It is also important to have available filter substances for the range between about 320 nm and about 400 nm, the so-called UVA region, since its rays can cause reactions in cases of photosensitive skin. It has been found that UVA radiation leads to damage of the elastic and collagen fibers of connective tissue, which results in premature aging of the skin, and is to be regarded as a cause of numerous phototoxic and photoallergic reactions. The harmful effect of UVB radiation can be intensified by UVA radiation.
To protect against rays of the UVA region, therefore, certain derivatives of dibenzoylmethane are used, the photostability of which is inadequate (Int. J. Cosm. Science 10, 53 (1988), the entire disclosure whereof is expressly incorporated by reference herein).
The UV radiation can, however, also lead to photochemical reactions, in which case the photochemical reaction products again interfere with the skin's metabolism.
Corresponding photochemical reaction products are primarily free-radical compounds, for example hydroxyl radicals. Undefined free-radical photoproducts which form in the skin itself can also result in uncontrolled secondary reactions due to their high reactivity. Furthermore, singlet oxygen, a non-free-radical excited state of the oxygen molecule, can also arise during UV irradiation, as can short-lived epoxides and many others. Singlet oxygen, for example, differs from triplet oxygen (free-radical ground state), which is normally present, by its increased reactivity. However, excited, reactive (free-radical) triplet states of the oxygen molecule also exist.
UV radiation is also a type of ionizing radiation. There is therefore the risk that ionic species will also form during UV exposure, which then for their part are able to interfere oxidatively with the biochemical processes.
In order to prevent these reactions, additional antioxidants and/or free-radical scavengers can be incorporated into the cosmetic or dermatological formulations.
It would be advantageous to have available cosmetically, dermatologically and pharmaceutically active substances and preparations as well as sunscreen formulations that are used for the prophylaxis and treatment of photosensitive skin, in particular photodermatoses, preferably the polymorphous light dermatosis.
Further terms for polymorphous light dermatosis are PLD, PLE, Mallorca acne and numerous other terms as given in the literature (e.g., A. Voelckel et al., Zentralblatt Haut-und Geschlechtskrankheiten (1989), 156, p. 2, the entire disclosure whereof is expressly incorporated by reference herein).
Antioxidants are mainly used as substances which protect against the deterioration of the preparations in which they are present. Nevertheless, it is known that in human and animal skin undesired oxidation processes can occur as well. Such processes play an important role in skin aging.
The article “Skin Diseases Associated with Oxidative Injury” in “Oxidative Stress in Dermatology”, p. 323 ff. (Marcel Decker Inc., New York, Basel, Hong Kong, Editor: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley/Calif.), the entire disclosure whereof is expressly incorporated by reference herein, discusses oxidative skin damage and its more direct causes.
Also for the reason of preventing such reactions, antioxidants and/or free-radical scavengers can be additionally incorporated into cosmetic or dermatological formulations.
The advantageous prophylactic and therapeutic effect of creatine in cosmetic and medical skin care is known per se. Creatine (from the Greek: =“the meat”) is characterized by the following structure:

Creatine is found in the myoserum of vertebrates in amounts of 0.05-0.4%, in small amounts also in the brain and blood. As a monohydrate, it is a colorless, crystalline powder. In aqueous solution, creatinine is formed. In the organism, it is formed by the transamidination of L-arginine on glycine to afford guanidinoacetic acid, and subsequent methylation thereof by means of S-adenosyl methionine (by guanidinoacetate methyltransferase). Creatine is regarded as an appetite-promoting constituent of beef and meat extract. The addition of creatine to the diet enhances physical performance.
The prior art is extensive on the cosmetic and dermatological uses of creatine. Thus, DE 100 32 964, the entire disclosure whereof is expressly incorporated by reference herein, describes the use of creatine and/or creatine derivatives in cosmetic or dermatological preparations for the treatment and prophylaxis of the symptoms of UV-induced and/or ozone-induced skin damage and of inflammatory and degenerative skin conditions.
JP 2000/247,866, the entire disclosure whereof is expressly incorporated by reference herein, describes skin cosmetics with a content of creatine and/or creatinine which can be used as a cream or as a milky lotion, where excellent skin care properties are attributed to the relevant preparations.
Furthermore, WO 00/33787, the entire disclosure whereof is expressly incorporated by reference herein, describes the use of creatinine as an effective constituent of deodorants.
Moreover, EP-A-565 010, the entire disclosure whereof is expressly incorporated by reference herein, describes hair growth and hair dye preparations with a content of creatinine phosphate.
Finally, U.S. Pat. No. 4,590,067 and EP-A-178 602, the entire disclosures whereof are expressly incorporated by reference herein, describe the use of creatine or creatinine to produce preparations with anti-inflammatory effect.
However, there is the disadvantage that in aqueous products creatine and creatinine crystallize easily, whereby crystals with non-cosmetic impression form and the effectiveness of the product is reduced.
It is desirable to find ways of avoiding the disadvantages of the prior art. In particular, the effect of remedying the damage associated with endogenous, chronological and exogenous skin aging and the prophylaxis should be durable, sustained and without the risk of side effects.
It would further be advantageous to find a form of administering creatine that is characterized by a reduced tendency to form creatine crystals.